title: Type I interferon signaling regulates Ly6C(hi) monocytes and neutrophils during acute viral pneumonia in mice.
abstract: Type I interferon (IFN-I) plays a critical role in the homeostasis of hematopoietic stem cells and influences neutrophil influx to the site of inflammation. IFN-I receptor knockout (Ifnar1⁻/⁻) mice develop significant defects in the infiltration of Ly6C(hi) monocytes in the lung after influenza infection (A/PR/8/34, H1N1). Ly6C(hi) monocytes of wild-type (WT) mice are the main producers of MCP-1 while the alternatively generated Ly6C(int) monocytes of Ifnar1⁻/⁻ mice mainly produce KC for neutrophil influx. As a consequence, Ifnar1⁻/⁻ mice recruit more neutrophils after influenza infection than do WT mice. Treatment of IFNAR1 blocking antibody on the WT bone marrow (BM) cells in vitro failed to differentiate into Ly6C(hi) monocytes. By using BM chimeric mice (WT BM into Ifnar1⁻/⁻ and vice versa), we confirmed that IFN-I signaling in hematopoietic cells is required for the generation of Ly6C(hi) monocytes. Of note, WT BM reconstituted Ifnar1⁻/⁻ chimeric mice with increased numbers of Ly6C(hi) monocytes survived longer than influenza-infected Ifnar1⁻/⁻ mice. In contrast, WT mice that received Ifnar1⁻/⁻ BM cells with alternative Ly6C(int) monocytes and increased numbers of neutrophils exhibited higher mortality rates than WT mice given WT BM cells. Collectively, these data suggest that IFN-I contributes to resistance of influenza infection by control of monocytes and neutrophils in the lung.
authors.affiliation: Mucosal Immunology Section, International Vaccine Institute, Seoul, South Korea.
authors.forename: Sang-Uk
authors.initials: SU
authors.lastname: Seo
authors.forename: Hyung-Joon
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Ko
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Byun
authors.forename: Baik Lin
authors.initials: BL
authors.lastname: Seong
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kweon
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation; D005260:Female; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology*; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D011014:Pneumonia / Q000209:etiology / Q000473:pathology; D011024:Pneumonia, Viral / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D053633:Receptor, Interferon alpha-beta / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; D012333:RNA, Messenger; D053633:Receptor, Interferon alpha-beta